The hepatotoxicity produced by furosemide in mice was evaluated by levels of plasma glutamic-pryruvic transaminase (GPT). Doses of 200 mg/kg s.c. or less did not elevate plasma levels of GPT. In contrast, doses of 300, 500, and 800 mg/kg increased plasma GPT greatly. Urine and bile were collected during successive 15- and 30-minute intervals for 180 minutes after injection of furosemile (50,200,300, or 500 mg/kg s.c.). Extrapolations to infinity were made on the basis of semi-logarithmic plots of excretion rates versus time and/or rectilinear plots of cumulative excretion versus time. About 23-33% of the injected furosemide was excreted unchanged in bile, at all doses tested. In contrast, the percent dose excreted unchanged in urine decreased steadily with increase in dose from 32.4% after 50 mg/kg to 15.9% after 200 mg/kg and 10.0% after 500 mg/kg. From about 40% after 50 mg/kg to about 66% after 500 mg/kg could not be accounted for by excretion in urine and bile and therefore probably represented metabolized furosemide. The impaired renal function and the increased metabolism are probably the major factors leading to hepatic necrosis after large doses of furosemide in the mouse.